Septic shock is a leading cause of mortality, accounting for 200,000 deaths and $10 billion in health care expenditures in the USA per annum. Current treatment regimens are supportive only, as there are no pharmaceuticals which halt or reverse disease progression. A key final common pathway of injury in septic shock is the production of nitric oxide and peroxynitrite. Inotek Corporation is developing a class of compounds, mercaptoalkylquanidines (MAGs), which potently inhibit NO formation and weakly scavenge peroxynitrite. The Specific Aim of the Phase 1 SBIR proposal is to design, synthesize, and quality analogs of the lead MAG compound, S-methyl-mercaptoethylquanidine, in order to achieve a 2-fold increased inhibition of NO formation and a 10-fold increase in peroxynitrite scavenging. Identification of a compound meeting these requirements would demonstrate commercial feasibility. Such an agent would possible represent the first effective treatment for septic shock and justify pre-clinical studies and a Phase 1 clinical trial to be supported by Phase 2 SBIR funding. PROPOSED COMMERCIAL APPLICATION: Development of a potent mercaptoalkylguanidine for th treatment of septic shock could result ultimately in commercialization of the first specific and effective agent for the clinical management of sepsis. Based upon current annual worldwide health care expenditures related to septic shock ($10 billion), annual gross revenues are estimated to be in excess of $1 billion.